Chapter 40 - Antiplatelets Flashcards
Normal platelet levels
150-350 x 10^9/L
Normal preventative measures of platelet aggregation
1) endothelium NO and prostacyclin 2) endothelial ADPase expression - degrade ADP
Platelet lifespan
8-10 days
Activation of platelets
1) exposed tissue factor 2) subendothelial collagen 3) vWF 4) fibronectin interact with glycoprotein on platelets platelets release ADP and thromboxane A2
Effect of ADP in platelet aggregation
1) ADP cross link platelets together
Thromboxane A2 in platelet aggregation
Vasoconstriction and further recruitment of platelets
Glycoprotein IIb/IIIa receptor
Exposes on surface of platelet when activated ligates divalent fibrinogen to bridge platelet promotes aggregation
Platelet function and molecular targets
FIGURE 40.1
ASA effect
1) irreversibly acetylates COX-1 (cyclooxygenase) 2) decrease prostaglandin H2 and thromboxane A2 3) prevent platelet aggregation 4) high doses of ASA inhibit COX-2 –> antinflammatory effects
Time to action of ASA after ingestion
1 hour enteric takes 3-4 hours chewing 20 min
Risk of bleeding with ASA treatment
1-3% / year
Allergy to ASA
0.3%
Clopidogrel key points
1) adenosine diphosphate receptor antagonist 2) thienopyridines 3) prodrug 4) activated by hepatic cytochrome 450 5) irreversibly inhibits P2Y12 ADP receptor on platelet
Dose of plavix
75mg - takes a day to have effect 300-600 mg loading - rapid onset 2 hours
GI hemorrhage with plavix
2%
drug interactions with plavix
PPI = inhibitor of CYP2C19 –> decrease ability of plavix to become activated
Ticlopidine
Block P2Y12 ADP receptor also via CYP450
Complication with ticlopidine
1) Neutropenia 2) Aplastic anemia 3) TTP
Ticagrelor action
1) binds ADP P2Y12 receptor non-competitively and reversibly 2) metabolized by CYP3A4
Dose of ticagrelor
180 mg loading then 60-90 mg BID
half life of ticagrelor
7-9 hours
Time to maximum inhibition of ticagrelor
2 hours
Prasugrel key points
irreversibly blocker P2Y12 use in TIA/stroke
Dose of prasugrel
60 mg then maintenance 10 mg daily
Cangrelor
reversibly bind P2Y12
Dose of cangrelor
30 mcg/kg bolus before PCI then 4 mcg/kg/min for 2 hours
time to action and half life of cangrelor
time to action < 2 min half life 3-6 minutes platelet function return to normal in 60 min after cessation
Glycoprotein IIB/IIIA inhibitors
Abciximab = monoclonal antibody eptifibatide, tirofiban = peptide antagonists
Dose of glycoprotein IIB/IIIA inhibitor
Abciximab 0.25 mg/kg before PCI then 0.125 mcg/kg/min Eptifibatide 180 mcg/kg then 2 mcg/kg/min Tirofiban 25 mcg/kg then 0.15 mcg/kg/min
Side effect with glycoprotein IIB/IIIA inhibitor
5% thrombocytopenia worst with abciximab
Half life of glycoprotein IIB/IIIA inhibitor
Abciximab - 30 min Eptifibatide 2.5 hours Tirofiban - 2 hours stop 2-4 hours before surgery; abciximab needs 12 hours because of slow dissociation
Dipyridamole effect
inhibit activity of adenosine deaminase and phosphodiesterase –> increase cAMP –> vasodilation and inhibit platelet aggregation
Aggrenox
200 mg Dipyridamole + 25 mg asa BID
Side effects of dipyridamole
1) headache 2) dizziness 3) skin rash 4) GI upset 5) chest pain
Dipyridamole half life
10-12 hours
Protease activated receptor 1 inhibitor
Vorapaxar inhibit thrombin-induced and thrombin receptor agonist peptide (TRAP) induced platelet aggregation half life 3-4 days takes 1 week to get 80% activity dose 2.5 mg daily with ASA Contraindicated in stroke, TIA, ICH
CAPRIE trial
1) plavix vs asa 2) 19185 patients 3) recent stroke, MI or PAD symptomatic 4) plavix had has slightly less risk of stroke, MI or death 5.32 vs 5.83
TRA 2P trial
Vorapaxar for secondary prevention of ischemic events Reduced hospitalization for acute limb ischemia and need for peripheral revasc
ACC/AHA guideline for perioperative management of CAD
FIGURE 40.4
